Optimum time to assess complete clinical response (CR) following chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance CisP/5FU in squamous cell carcinoma of the anus: Results of ACT II.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
Robert Glynne-Jones ◽  
Roger James ◽  
Helen Meadows ◽  
Rubina Begum ◽  
David Cunningham ◽  
...  
Keyword(s):  
Absolute Difference ◽  
Optimal Time ◽  
Relapse Free Survival ◽  
Tumour Site ◽  
Optimum Time ◽  
Free Survival ◽  
Node Negative ◽  
Time Points ◽  
Risk Of Progression

4004 Background: In the ACT I trial, relapse-free survival was improved with CRT compared to RT alone, but the CR rate at 6 weeks was similar (39% CRT, 30% RT alone; p=0.08). Most studies assessed CR between 6 and 12 weeks following completion of CRT. We investigated the association between observation of CR at 3 different time-points and progression-free and overall survival (PFS, OS), to determine the optimal time to assess this early endpoint. Methods: ACT II recruited 940 pts between 2001 and 2008. It compared, in a factorial design, CisP versus MMC when combined with 5-FU CRT, and two cycles of maintenance chemotherapy versus no maintenance. CR (complete absence of tumour and node negative) was assessed by rectal exam or imaging at 11, 18 and mandated CT at 26 weeks after the start of CRT. Median follow-up was 5 years. Pts were excluded from analysis if assessment was not done/ missing at one or more time points (n=245). Data from 695 pts were analysed. Results: Pt characteristics (all 940) median age 58 years; tumour site – canal (84%), margin (14%); stage T1-T2 (52%), T3-T4 (46%); N+ (32%), N0 (62%). CisP did not improve OS (HR: 0.96, p=0.89) or PFS (HR: 0.85, p=0.43) compared to MMC. This is consistent with the lack of an absolute difference at 18 and 26 weeks, but not at 11 weeks (where a difference was found). CR patients (compared to not-CR) had a significantly lower risk of progression/death. The association between these outcomes and response was strongest at 26 weeks. 202/695 (29%) pts not in CR at 11 weeks were CR at 26 weeks. Conclusions: 29% of pts not in CR at 11 weeks achieved CR at 26 weeks. Early surgical salvage would not have been appropriate for these pts. We recommend assessment at 26 weeks in future trials. [Table: see text]

Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.

1993 ◽  
Vol 11 (11) ◽  
pp. 2090-2100 ◽  
Author(s):  
P P Rosen ◽  
S Groshen ◽  
D W Kinne ◽  
L Norton
Keyword(s):  
Breast Carcinoma ◽  
Adjuvant Therapy ◽  
Lobular Carcinoma ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Contralateral Carcinoma ◽  
Tumor Types ◽  
Favorable Group

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.

scholarly journals AB0509 SUSPENSIVE EFFICACY OF TOCILIZUMAB IN TREATMENT-NAÏVE PATIENTS WITH TAKAYASU ARTERITIS: TOCITAKA FRENCH PROSPECTIVE MULTICENTER OPEN-LABELLED TRIAL.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1552.3-1552
Author(s):  
A. Mekinian ◽  
D. Saadoun ◽  
J. C. N. F. [email protected] ◽  
I. Q. M. F. [email protected] ◽  
P. Jégo ◽  
...  
Keyword(s):  
Disease Activity ◽  
Takayasu Arteritis ◽  
Immunosuppressive Drugs ◽  
Relapse Free Survival ◽  
Research Support ◽  
Free Survival ◽  
Treatment Naïve ◽  
Steroid Sparing

Objectives:To assess long term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).Methods:In this multicenter, prospective, open-labelled trial, we aim to evaluate the benefit of adding tocilizumab to steroids in treatment-naïve patients with TAK, on discontinuation of steroids after 6 months of tocilizumab treatment, and to assess relapse-free survival following tocilizumab discontinuation.Results:Thirteen patients with TAK were included, with a median age of 32 years [19-45] and 12 (92%) females. Six (54%) patients met the primary end-point. Among 11 (85%) patients which achieved remission at 6 months, 6 (54%) have reached primary endpoint.. Among the 5 remaining patients which continued steroids, 3 had a prednisone-equivalent dosage < 5mg/day. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3-4] at baseline, versus 1 [0-2] after 6 months; p <0.001), ITAS-2010 score (5 [2-7] versus 3 [0-8]; p = 0.002), and ITAS-A score (7 [4-10] versus 4 [1-15]; p = 0.0001)]. All patients discontinued tocilizumab after 7 infusions, and no other immunosuppressive drugs was introduced, except for 1 patient which received methotrexate. After 9 and 12 months, respectively 7 (54%) and 6 (50%) patients achieved remission with less than 7.5 mg/day of prednisone, and 9 (69%) and 9 (75%) with doses <10 mg/day. During the 12 months follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.No severe AEs were considered related to study treatment and none required tocilizumab interruption or dose reduction. No deaths have occurred during the study period.Conclusion:Tocilizumab seems an effective steroid sparing therapy in TAK but its effect appears to be suspensive.Disclosure of Interests:Arsene Mekinian: None declared, david Saadoun: None declared, [email protected] [email protected]: None declared, [email protected] [email protected]: None declared, Patrick Jégo: None declared, [email protected] [email protected]: None declared, wxv wxv: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mathieu Vautier: None declared, [email protected]>; [email protected]>;: None declared, Patrice cacoub: None declared, olivier fain: None declared

scholarly journals Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I–II nasopharyngeal carcinoma: a nest case-control study

2021 ◽  
Author(s):  
Bei-Bei Xiao ◽  
Qiu-Yan Chen ◽  
Xue-Song Sun ◽  
Ji-Bin Li ◽  
Dong-hua Luo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stage I ◽  
Relapse Free Survival ◽  
Retropharyngeal Lymph Node ◽  
Free Survival ◽  
Pet Ct ◽  
Pre Treatment

Abstract Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.

scholarly journals Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

scholarly journals Two-Hour Post-Load Plasma Glucose, a Biomarker to Improve the GRACE Score in Patients without Known Diabetes

Cardiology ◽  
2020 ◽  
Vol 145 (9) ◽  
pp. 553-561
Author(s):  
Sudipta Chattopadhyay ◽  
Anish George ◽  
Joseph John ◽  
Thozhukat Sathyapalan
Keyword(s):  
Plasma Glucose ◽  
Information Criteria ◽  
Prognostic Models ◽  
Ratio Test ◽  
Cardiac Events ◽  
Free Survival ◽  
Time Points ◽  
Coronary Syndrome ◽  
Akaike’S Information Criteria

Objective: To assess improvement in predictive performance of Global Registry of Acute Coronary Events risk score (GRS) by addition of a glucose matrix. Methods: 1,056 acute coronary syndrome (ACS) survivors without known diabetes had pre-discharge fasting (FPG) and 2-h post-load plasma glucose (2h-PG) measured. GRS was calculated. Major adverse cardiac events (MACE; death and non-fatal myocardial infarction) were recorded during follow-up. Cox proportional hazard regression predicted event-free survival. Likelihood ratio test, Akaike’s information criteria, continuous net reclassification index (NRI>0), and integrated discrimination improvement (IDI) were used to test the additional prognostic value of glycaemic indices over GRS. Results: During a median follow-up of 36.5 months, 211 MACEs (20.0%), 96 deaths (9.1%), and 115 non-fatal re-infarctions (10.9%), occurred. 2h-PG, but not FPG, independently predicted MACE-free survival at all time points (HR 1.08, 95% CI 1.03–1.13, p = 0.002, at 3 years). Risk of MACE increased by 8–11% with every 1 mmol/L rise in 2h-PG. 2h-PG significantly improved the prognostic models containing GRS. Models containing GRS and 2h-PG yielded lowest corrected Akaike’s information criteria compared to that with only GRS. 2h-PG, but not FPG, improved NRI>0 (NRI>0 0.169, p = 0.028 at 3 years) and IDI (IDI of 0.66%, p = 0.018 at 3 years) significantly at all time points during the follow-up. Conclusions: 2h-PG, but not FPG, improves performance of GRS-containing models in predicting post-ACS prognosis in the short to medium term.

Randomized cooperative study of perioperative chemotherapy in breast cancer.

1995 ◽  
Vol 13 (11) ◽  
pp. 2712-2721 ◽  
Author(s):  
M R Sertoli ◽  
P Bruzzi ◽  
P Pronzato ◽  
P Queirolo ◽  
D Amoroso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Preliminary Evidence ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Negative ◽  
Significant Survival ◽  
Significant Difference ◽  
Estrogen Receptor Negative

PURPOSE The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients. PATIENTS AND METHODS Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy. RESULTS At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing. CONCLUSION This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.

Pepsinogen C is a new prognostic marker in primary breast cancer.

1995 ◽  
Vol 13 (1) ◽  
pp. 54-61 ◽  
Author(s):  
F Vizoso ◽  
L M Sánchez ◽  
I Díez-Itza ◽  
A M Merino ◽  
C López-Otín
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Survival Duration ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Pepsinogen C ◽  
Node Positive

PURPOSE Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

Follow-up Analysis of a Randomized Comparison of Prolonged Myelosuppressive Maintenance Therapy Versus Intensive Consolidation Therapy as Postremission Therapy in AML.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1056-1056
Author(s):  
Utz O. Krug ◽  
Maria Cristina Sauerland ◽  
Bernhard J Woermann ◽  
Wolfgang Berdel ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Postremission Therapy ◽  
To Receive

Abstract Abstract 1056 Poster Board I-78 Introduction: We previously showed that a prolonged myelosuppressive maintenance chemotherapy was superior to S-HAM as a postremission therapy in patients > 16 years of age with AML after a TAD-HAM double induction therapy and TAD consolidation chemotherapy with regard to relapse-free survival (RFS) and borderline significance of the overall survival (OS) in responding patients (Buchner et al., JCO 2003, 21:4496-4504). Here we present long-term follow-up data with a median follow-up of 7.9 years from diagnosis and 7.1 years from the date of complete remission. Patients and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were upfront randomized in the AMLCG1992 study of the German AML Co-operative Group to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] x 6 (HAM in patients ≥ 60 years only in case of blast persistence on day 16 of therapy) induction, TAD consolidation, and monthly maintenance with cycles of cytarabine combined with either daunorubicin (course 1), 6-thioguanine (course 2), cyclophosphamide (course 3), and again 6-thioguanine (course 4), and restarting with course 1 for 3 years, or to receive TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) x 8 instead of maintenance. Results: A total of 576 patients (69.2%) achieved a complete remission (CR) those were 294 of 429 (68.5%) patients randomized to receive maintenance and 282 of 403 (70.0%) patients randomized to receive intensive consolidation S-HAM (p=n.s.). 190 patients received maintenance therapy as intended and 135 patients received an intensive consolidation therapy as intended. This prolonged follow-up analysis verified the superior relapse-free survival in all patients in the maintenance arm (10-year RFS 30.0 ± 5.6 versus 19.9 ± 6.1 %, p = 0.015). Stratified by age, the 10-year RFS was superior in younger patients < 60 years (36.9 ± 7.1 versus 25.2 ± 8.0 %, p = 0.038) and borderline significant in elderly patients (17.2 ± 4.5 versus 6.8 ± 6.2 %, p = 0.075). A subgroup analysis of known risk groups (lactate dehydrogenase (LDH) level < 700U/l versus ≥ 700U/l at diagnosis, cytogenetic risk profile, bone marrow blasts on day 16 after the start of the induction therapy) revealed a superior RFS in the subgroup of patients with LDH level > 700 U/l at diagnosis (33.5 ± 12.3 versus 18.2 ± 9.5 %, p = 0.043). This superior RFS also translated into a superior 10-year relapse-free interval (RFI) of all responding patients in the maintenance arm (35.7 ± 6.3 versus 27.6 ± 5.9 %, p = 0.015) with borderline significance in younger patients (42.9 ± 7.4 versus 35.0 ± 7.4 %, p = 0.053) and a significant difference in elderly patients (20.6 ± 10.0 versus 8.4 ± 7.5 %, p = 0.043). In this updated analysis, there was a trend, but no significant difference in the OS (maintenance arm: 10-year OS 24.3 ± 4.8, intensive consolidation arm: 19.7 ± 4.7 %, p = 0.148), and we verified a trend for a better OS in responding patients for the maintenance arm (10-year OS in responding patients 33.6 ± 7.5 versus 28.5 ± 6.2 %, p = 0.093). The event-free survival (EFS) also showed a trend towards better EFS in the maintenance arm (10-year EFS 20.7 ± 4.2 versus 14.8 ± 4.1 %, p = 0.082) which was significant in elderly patients (10-year EFS 10.5 ± 5.5 versus 3.9 ± 3.7 %, p = 0.044). Discussion: This updated analysis with a long-term follow-up of median 7.9 years from diagnosis and 7.1 years from CR verified the superior RFS and the trend for enhanced OS in responding patients. These results suggest the superiority of a prolonged monthly myelosuppressive maintenance therapy as compared to intensive consolidation S-HAM after TAD-HAM induction and TAD consolidation. Disclosures: No relevant conflicts of interest to declare.

Does ATRA Confirm to Play a Role in the Better Relapse Free Survival of Infants with Acute Lymphoblastic Leukemia?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1515-1515
Author(s):  
Larisa Fechina ◽  
Egor Shorikov ◽  
Olga Streneva ◽  
Olga Khlebnikova ◽  
Igor Vyatkin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Molecular Mechanisms ◽  
Treatment Approach ◽  
Lymphoblastic Leukemia ◽  
Relapse Free Survival ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Abstract 1515 Treatment achievements in infant's acute lymphoblastic leukemia (ALL) are still very modest. Despite of many attempts, the creation of novel, based on the molecular mechanisms, clinically approved and safe therapy strategies for this group of patients (pts) seems to be slow, so far. We also have developed a new treatment approach for infants with acute leukemia – MLL-Baby protocol, which includes 1 or 2 weeks ATRA consecutive courses at the dosing schedule of 25 mg/m2/d adjusted to age, started immediately after induction completion, alternating with standard chemotherapy and/or simultaneously applied with re-inductions. Rationale for ATRA application and MLL-Baby details were introduced in our previous report (ASH 2007 Abstract #2828). We have described there a small group of 19 primary diagnosed ALL infants, who underwent MLL-Baby protocol treatment in comparison to the group treated by standard chemotherapy with 20 months (mo.) median of follow up. ATRA-containing regimen has been shown well tolerated and improved early relapse free survival (RFS) significantly. Aim. To re-assess the ATRA efficacy in more representative group of pts with longer time of follow up. From September 2003 108 pts with primary ALL younger 12 mo. were non-randomly allocated either to ATRA (+) treatment approach (MLL-Baby) – 75 pts or ATRA (-) standard chemotherapy (mainly ALL-MB) – 33 pts due to decision of the treating physicians from 24 participating clinics in Russia and Belarus. Parents' informed consent was signed in all cases. The trial was approved by Ethics Committees. Both ATRA (−) and ATRA (+) groups were similar by the initial characteristics: median age 6 (1–11) and 6 (0–11) mo.; m/f ratio 12/21 and 25/50; initial WBC 96,7 (0,7–940) and 83,9 (1,6–2058) per microliter respectively, although CNS involvement seems to be more frequent in ATRA (+) group: 4 (12%) and 18 (24%) pts correspondingly. MLL rearrangements (MLL pos.) were found in 15 (53,6%) from 28 examined ATRA (−) pts and in 53 (70,7%) from 75 ATRA (+) pts. BI phenotype predominance was evident in ATRA (+) group - 39 (52,7%) out of 74 examined pts. The number of pts who have achieved CR was equally high in both schedules: 28 (84,9%) and 67 (89,3%) but the relapses rates remains significantly different: 16 (57,1%) and 16 (23,8%) pts in ATRA (-) and ATRA (+) groups respectively (p=0,001). Eight years RFS is 0,36 ± 0,08 and 0,59 ± 0,06 (p=0,02); cumulative incidence of relapses (RCI) is 0,62 ± 0,01 and 0,31 ± 0,004 (p=0,03) in ATRA (−) and ATRA (+) groups correspondingly, although EFS: 0,54 ± 0,06 vs. 0,33 ± 0,08 (p=0,17) and OS: 0,59 ± 0,06 vs. 0,36 ± 0,08 (p=0,09), median of follow up - 36 mo. (2 - 105), did not differ significantly between 2 groups ATRA (+) and ATRA (−) respectively due to the high proportion of induction and remission deaths. Among 75 pts treated by MLL-Baby – 7 (9,3%) died in induction and 7 (10,4%) out of 67 pts who achieved CR died in remission with median time to death – 2 mo., mostly because of severe infections. Out of 46 MLL pos. pts from ATRA (+) group who achieved CR, 14 (30%) pts relapsed, RFS is 0,59 ± 0,08 and RCI 0,40 ± 0,007. In contrast, in ATRA (−) group the relapse incidence in MLL pos. pts was very high - 12 (80%) out of 15 pts who achieved CR (p=0,008), RFS is 0,20 ± 0,10 (p=0,01) and RCI 0,80 ± 0,01 (p=0,02) correspondingly. In univariate analysis the following risk-factors: age < 6 mo. (p=0,001); MLL rearrangements (p=0,004) and dexamethasone response on Day 8 (p=0,01) have a significant negative impact on EFS in group of pts treated by MLL-Baby. Cox-regression analysis confirms the negative value of the same risk-factors: MLL pos. status with Hazard Ratio (HR) 3,8 (95% CI 1,32-10,9) p=0,01; age HR 3,18 (95%CI 1,5–6,8) p=0,003 and Day 8 response HR 3,16 (95% CI 1,4–7,1) p=0,005. Conclusions. The updated results in our cohort of 75 patients demonstrated that ATRA confirms effectiveness in the relapses prevention in infants suffering from ALL, if used in combination with standard chemotherapy without any escalation and bone marrow transplantation. Although the molecular mechanisms of ATRA effect are still poorly understood and need to be deeply explored, it might be recommended for randomization within representative international studies, particularly to the MLL rearranged infant's ALL. Great efforts in non-relapse mortality reduction should be applied by all participating clinics. Disclosures: No relevant conflicts of interest to declare.

Cryopreservation of Peripheral Blood Stem Cells From Matched Related and Unrelated Donors Is Associated with Delayed Neutrophil and Platelet Engraftment but Does Not Influence Relapse-Free Survival

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2998-2998
Author(s):  
Patrick G Medd ◽  
Sandeep Nagra ◽  
Daniel Hollyman ◽  
Charles F. Craddock ◽  
Ram Malladi
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Lymphoid Malignancy ◽  
Relapse Free Survival ◽  
Peripheral Blood Stem Cells ◽  
Free Survival ◽  
Blood Stem Cells ◽  
Neutrophil Engraftment

Abstract Abstract 2998 Cryopreservation of peripheral blood stem cells (PBSC) for allogeneic transplantation (allo-SCT) has potential advantages including ensuring an adequate stem cell dose is available prior to commencing transplant conditioning and allowing more flexible transplant scheduling. Concerns that cryopreservation may impair engraftment have, however, limited its use. In addition, no published series have examined cryopreservation of matched unrelated donor (MUD) PBSC. In this study, we assessed engraftment and survival following allo-SCT using cryopreserved PBSC. Seventy-six allo-SCT using cryopreserved PBSC were assessed: 57 from HLA matched family donors and 19 from MUD where HLA allelic match was 10/10 (n=14) or 9/10 (n=5). Transplants were performed between 2004 and 2010. Indications for allo-SCT were myeloid malignancy (n=50) or lymphoid malignancy (n=26). Disease was early phase in 51 (67.1%) and late phase in 25 (32.9%) patients. Conditioning was myeloablative (MAC) in 27 and reduced intensity (RIC) in 49 patients, 49 patients received in vivo T cell depletion with alemtuzumab or anti-thymocyte globulin. Median follow-up (FU) of survivors was 41 months. Comparison was made against a broadly matched control group comprising 79 allo-SCT using fresh PBSC. Cumulative incidence of neutrophil engraftment to >0.5 × 109/L at day 14 was (95% confidence interval (CI)) 73.3% (61.–82) vs 92.3% (83.4–96.5) for cryopreserved vs fresh PBSC respectively. Neutrophil engraftment was significantly delayed (P=0.00031, Log-rank test) in the cryopreserved group but neutrophil engraftment at day 30 was identical at 99% in both groups. Platelet (plt) engraftment to >50 × 109/L at day 14 was 27.6% (18.8–38.1) vs 58.9% (47.1–69) for cryopreserved vs fresh PBSC respectively, P<0.0001. Cumulative incidence of plt engraftment at day 30 was 72.3% (60.3–81.2) vs 96.2% (87.4–98.9) for cyropreserved and fresh PBSC respectively. In multivariate analysis delayed neutrophil engraftment was associated with cryopreservation (hazard ratio (HR)=1.59, 95% CI 1.2–2.13, P=0.0014), MAC (HR=1.67, 95%CI 1.22–2.3, P=0.0015) and lymphoid malignancy (HR=1.49, 95% CI 1.11–2, P=0.0077). Delayed plt engraftment was associated with cryopreservation (HR=2.17, 95% CI 1.49–3.13, P<0.0001) and related donor transplant (HR=1.46, 95% CI 1.05–2, P=0.025). Eight patients, 6 in the cryopreserved and 2 in the fresh PBSC group required CD34 selected PBSC ‘top-up’ for primary engraftment failure, 5 of whom (4 cryopreserved, 1 fresh) were alive at last follow-up. One patient in the fresh and none in the cryopreserved PBSC group experienced late secondary graft failure. Relapse-free survival at 2 years was 40.7% (30.4–54.4) vs 50.2% (39.6–63.6) P=0.42 for cryopreserved vs fresh PBSC respectively. There were no significant differences in relapse incidence, transplant-related mortality, incidence of grades II-IV acute graft-vs-host disease or extensive chronic GvHD between cryopreserved and fresh PBSC. Whilst cryopreservation of PBSC for allo-SCT in both matched related and MUD allo-SCT is associated with significantly delayed neutrophil and platelet engraftment, only delayed platelet engraftment is likely to be of clinical significance. Survival was comparable to allo-SCT using fresh PBSC. In lieu of evidence from prospective trials, PBSC cryopreservation should be considered as an option in selected patients for whom its benefits outweigh the risks of delayed engraftment. Disclosures: Craddock: Celgene: Honoraria, Research Funding.

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